Project Summary Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, seizures, disturbed behavior and little/no speech. Robust longitudinal, prospectively collected, natural history data are the bedrock for the design of clinical trials, including selection of appropriate outcome measures. This AS Natural History Study seeks to address the unmet needs listed below by introducing new outcome measures, including those suggested by pharmaceutical company actively developing treatments for AS: (i) Current outcome measures do not adequately assess communication skills of individuals with AS, including the use of augmentative and alternative communication (AAC) devices. (ii) Anxiety, a debilitating symptom in some individuals with AS, has not been examined systematically. (iii) The motor and language impairments faced by individuals with AS negatively impacts their scores on the most widely-used assessment tool (Bayley Scales of Infant Development, BSID) and results in an underestimation of their abilities. (iv) Evaluation of treatment effects is limited by an inadequate number of validated outcome measures. (v) The natural history of AS in adults is poorly understood due to small number of adult participants. The overall goal is to increase understanding of the long-term natural history of AS and obtain AS-specific norms for outcome measures that can be used in clinical trials, to ultimately improving their care. The specific aims are: Aim 1: To conduct a prospective, longitudinal natural history study of AS in both children and adults, using investigator-observed and parent-reported outcome measures that will be useful for future clinical trials. Aim 2: Adapt the BSID for the AS population, by lessening the bias introduced by motor and language impairments, and pilot its use. Exploratory Aim: To assess the feasibility of using video recordings obtained by caregivers in the participant's natural environment to study the abilities of individuals with AS to use AAC devices. Participants will be enrolled (at 3 physical sites and via remote participation) for annual assessments including medical/developmental history, physical examination (on-site participants), and a battery of developmental and behavioral measures. For participants at the physical sites, a modified version of the BSID, which removes the penalty in the cognitive domain introduced by fine motor impairments and speed of accomplishment, and credits non-verbal communication modalities in the expressive language domain, will be administered. Video recordings of participants will be edited and scored by an expert in the use of AAC devices.